title: Parkin overexpression ameliorates hippocampal long-term potentiation and β-amyloid load in an Alzheimer's disease mouse model.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a severe decline of memory performance. A widely studied AD mouse model is the APPswe/PSEN1ΔE9 (APP/PS1) strain, as mice exhibit amyloid plaques as well as impaired memory capacities. To test whether restoring synaptic plasticity and decreasing β-amyloid load by Parkin could represent a potential therapeutic target for AD, we crossed APP/PS1 transgenic mice with transgenic mice overexpressing the ubiquitin ligase Parkin and analyzed offspring properties. Overexpression of Parkin in APP/PS1 transgenic mice restored activity-dependent synaptic plasticity and rescued behavioral abnormalities. Moreover, overexpression of Parkin was associated with down-regulation of APP protein expression, decreased β-amyloid load and reduced inflammation. Our data suggest that Parkin could be a promising target for AD therapy.
authors.affiliation: State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Hong
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Guoqi
authors.initials: G
authors.lastname: Zhu
authors.forename: YingHan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Haiyun
authors.initials: H
authors.lastname: Suo
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.forename: Dongping
authors.initials: D
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Yufang
authors.initials: Y
authors.lastname: Huang
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.forename: MinJuan
authors.initials: M
authors.lastname: Bian
authors.forename: Zhejin
authors.initials: Z
authors.lastname: Sheng
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
authors.forename: Houyan
authors.initials: H
authors.lastname: Song
authors.forename: Thomas
authors.initials: T
authors.lastname: Behnisch
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D017774:Long-Term Potentiation; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D016708:Synaptophysin / Q000378:metabolism; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D016564:Amyloid beta-Protein Precursor; D016708:Synaptophysin; C569015:Syp protein, mouse; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D046988:Proteasome Endopeptidase Complex